A variety of osteogenic proteins have been shown to induce either cartilage or bone formation in vivo. For example, BMP-2 has been found to be safe and feasible for use in the treatment of fractures and for use in bone regeneration. Certain recombinant osteogenic proteins have also been extensively studied and have demonstrated significant osteogenic activity in several models of bone formation.
The therapeutic utility of BMP-2 and other osteogenic proteins is widely recognized. It is contemplated that the availability of the pure BMP-2 protein would revolutionize orthopedic medicine, certain types of plastic surgery, and various periodontal and craniofacial reconstructive procedures.
Currently, there are two major methods for the production of osteogenic proteins. The first involves extracting osteogenic proteins from demineralized cortical bone. The second method involves expressing osteogenic proteins using a recombinant expression system, and isolating the recombinant protein.
Both methods of production have significant drawbacks. The first method of purifying osteogenic proteins from bone is costly, time-consuming, and generally produces low yield. The second method enables production of osteogenic proteins with higher yield, but obtaining therapeutic amounts of recombinant proteins may be cost prohibitive in certain situations.
Furthermore, recombinant systems may lack additional factors that are present in tissue-derived protein preparations.
There exists a need for preparing osteogenic protein preparations, which combines the benefit of high yield and activity and minimizing cost.
U.S. Pat. No. 7,172,629 to McKay describes osteogenic paste compositions with enhanced osteoinductive properties for use in bone repair. The composition include a resorbable paste carrier, a more slowly resorbed mineral matrix, and Bone Morphogenetic Protein (BMP) or other osteogenic factor, which enable increased osteoinductive activity while retaining a scaffold for the formation of new bone at the implant site. Methods for making and methods for therapeutic use of the compositions are also described.
U.S. Pat. No. 5,236,456 to O'Leary et al. describes osteogenic compositions obtained from demineralized bone tissue. The osteogenic composition is compatible with many types of materials which can be introduced in the composition to enhance or augment bone repair or reconstruction. O'Leary further contemplates the addition of demineralized bone powder and other osteogenic, osteoinductive and/or osteoconductive substances such as bone morphogenic proteins (BMP) and/or any of numerous other medically useful substances to the osteogenic composition.
U.S. Pat. No. 7,132,110 to Kay et al. describes osteogenic compositions prepared by a process including the steps of subjecting demineralized bone to an extraction medium to produce an insoluble extraction product and a soluble extraction product, separating the insoluble extraction product and the soluble extraction product, drying the soluble extraction product to remove all or substantially all of the moisture in the soluble extraction product, and combining the dried soluble extraction product of step c) with demineralized bone particles.
U.S. Pat. No. 7,189,392 to Kim et al. describes an injectable formulation for delivery of osteogenic proteins. The formulation comprises a pharmaceutically acceptable admixture of an osteogenic protein; and formulations comprising osteogenic protein, hyaluronic acid derivatives and tricalcium phosphate. Methods for formulating porous injectable gels and pastes from hyaluronic acid are also disclosed.
U.S. Pat. No. 7,041,641 to Rueger et al. describes osteogenic devices and uses thereof for repair of bone and cartilage defects. The devices and methods promote formation of repair tissue with using less osteogenic protein than other devices. Defects repairable with the devices include critical size defects, non-critical size defects, non-union fractures, fractures, osteochondral defects, subchondral defects, and defects resulting from degenerative diseases such as osteochondritis dissecans.
U.S. Pat. No. 6,949,251 to Dalal et al. describes a porous a porous β-tricalcium phosphate material for bone implantation. The pore size diameter is in the range of 20-500 μm. The porous β-TCP material provides a carrier matrix for bioactive agents and can form a moldable putty composition upon the addition of a binder. Preferably, the bioactive agent is encapsulated in a biodegradable agent. Dalal also describes a kit and an implant device comprising the porous β-TCP, and a bioactive agent and a binder. The invention also provides an implantable prosthetic device comprising a prosthetic implant having a surface region, a porous β-TCP material disposed on the surface region and optionally comprising at least a bioactive agent or a binder. Methods of producing the porous β-TCP material and inducing bone formation are also provided.
U.S. Pat. No. 6,919,308 to Oppermann et al. describes osteogenic devices comprising a matrix containing substantially pure natural-sourced mammalian osteogenic protein; DNA and amino acid sequences for novel polypeptide chains useful as subunits of dimeric osteogenic proteins; vectors carrying sequences encoding these novel polypeptide chains and host cells transfected with these vectors; methods of producing these polypeptide chains using recombinant DNA technology; antibodies specific for these novel polypeptide chains; osteogenic devices comprising these recombinant proteins in association with an appropriate carrier matrix; and methods of using the osteogenic devices to mimic the natural course of endochondral bone formation in mammals.
U.S. patent publication No. 20070003593 by Wironen et al. describes an orthopedic bone paste useful for the repair of non-union fractures, periodontal ridge augmentation, craniofacial surgery, implant fixation, impaction grafting, or any other procedure in which generation of new bone is deemed necessary. The orthopedic composition comprises an osteogenic compound in a gelatin matrix. The osteogenic compound may include demineralized bone matrix (DBM), bioactive glass ceramic, bioactive ceramic, calcium phosphate ceramic, hydroxyapatite, hydroxyapatite carbonate, corraline hydroxyapatite, calcined bone, tricalcium phosphate, or like material. The composition may further include bone morphogenetic protein, TGF-, PDGF, or mixtures thereof.
U.S. patent publication No. 20040072322 by Thorne describes methods for purifying osteogenic proteins from calcified bone. The method includes a demineralization process, a protein extraction process, a high molecular weight ultrafiltration process, a low molecular weight ultrafiltration process, and a recovery process. The high and low ultrafiltration processes preferably select proteins having a nominal molecular weight between approximately 8 kilodaltons and approximately 50 kilodaltons. Processes of the present invention may be used to recover osteogenic proteins from bone demineralization waste streams.
U.S. patent publication No. 20050205498 by Sowemimo-Coker describes methods and compositions prepared from a cell concentrate, such as, for example, an osteogenic cell concentrate, from a physiological solution, such as bone marrow aspirate, blood, or a mixture thereof. The invention also provides methods and compositions utilizing two physiological solution-processing techniques, particularly in a point of care environment, wherein centrifugation is not employed.
U.S. patent publication No. 20060246150 by Thorne describes a composition for the induction of bone growth. The composition includes a substrate, bone growth protein; and sources of calcium and phosphate. The composition is acidic, which promotes high activity of the bone growth protein. The calcium and phosphate sources can be provided as an acidic calcium phosphate salt. Also disclosed are methods of the making the composition and methods of using it.
U.S. patent publication No. 20030185803 by Kadiyala describes a musculoskeletogenic MSG graft composite made from whole bone marrow aspirate (BMA) having native levels of musculoskeletal progenitor cells MSPCs. The composite includes a suspension of fractionated BMA comprising MSPCs present at a level greater than their native level in whole BMA, and red blood cells (RBCs) present at a level less than their native level in whole BMA, and a porous sterile matrix having an average pore size of at least 20 μm.
U.S. patent publication No. 20020082697 by Damien describes collagen-based osteogenic materials having useful shaping and handling properties and which are easier for health care practitioners to use than conventional implantable osteogenic materials. The shaped implantable compositions or devices also provide a suitable matrix for the release of osteogenic substances and other desirable biologically active agents at the site of implantation to promote bone growth.
The aforementioned prior art references are incorporated by reference as though fully set forth herein.